18-57483039-A-C

Variant names:

• chr18-57483039-A-C
• rs629737
• NM_004852.3:c.*6316A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004852.3(ONECUT2):​c.*6316A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,898 control chromosomes in the GnomAD database, including 11,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11873 hom., cov: 30)
  • Exomes 𝑓: 0.34 (28 hom.)
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711
• Publications: 8 publications found

Genes affected

ONECUT2 (HGNC:8139): (one cut homeobox 2) This gene encodes a member of the onecut family of transcription factors, which are characterized by a cut domain and an atypical homeodomain. The protein binds to specific DNA sequences and stimulates expression of target genes, including genes involved in melanocyte and hepatocyte differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ONECUT2	NM_004852.3	c.*6316A>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000491143.3	NP_004843.2
ONECUT2	XM_047437947.1	c.*6527A>C		3_prime_UTR_variant	Exon 3 of 3		XP_047293903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ONECUT2	ENST00000491143.3	c.*6316A>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_004852.3	ENSP00000419185.2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58629 AN: 151354 Hom.: 11832 Cov.: 30

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.345 AC: 149 AN: 432 Hom.: 28 Cov.: 0 AF XY: 0.373 AC XY: 97 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.345 AC: 147 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.388 AC: 58734 AN: 151466 Hom.: 11873 Cov.: 30 AF XY: 0.396 AC XY: 29321 AN XY: 74014

African (AFR) AF: 0.474 AC: 19558 AN: 41236

American (AMR) AF: 0.468 AC: 7126 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1005 AN: 3456

East Asian (EAS) AF: 0.483 AC: 2489 AN: 5150

South Asian (SAS) AF: 0.408 AC: 1959 AN: 4804

European-Finnish (FIN) AF: 0.390 AC: 4064 AN: 10412

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21303 AN: 67886

Other (OTH) AF: 0.391 AC: 821 AN: 2102

Alfa AF: 0.361 Hom.: 2989

Bravo AF: 0.399

Asia WGS AF: 0.428 AC: 1487 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.7
DANN	Benign	0.73
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs629737; hg19: chr18-55150271; COSMIC: COSV72203469;